A new study elucidates the role that a protein called TFIIB plays in supporting the activity of p53, a protein that helps suppress tumors

BUFFALO, N.Y. -- In a new study, University at Buffalo
scientists describe the role that a protein called TFIIB plays in
helping cells repair DNA damage, a critical function for preventing
the growth of tumors.

The research appeared
online on Oct. 30 in the Proceedings of the National Academy of
Sciences (PNAS) Early Edition.

TFIIB, short for "transcription factor II B," is a protein that
binds to DNA in cells to initiate the process of transcription,
which is critical for building new proteins.

When DNA damage occurs, TFIIB is altered in a way that halts
general transcription, enabling a cell to give priority to repair,
the researchers found. With the shut-down in effect, cells are able
to prioritize the important functions carried out by a
tumor-suppressing protein called p53, said lead author Jayasha
Shandilya, a postdoctoral researcher in UB's Department of
Biological Sciences.

"P53 is a very important protein in humans and other
multicellular organisms," Shandilya said. "It is called the
'guardian of the genome' because it helps maintain the stability of
the genome."

About half of cancer cases involve a mutation or deletion of the
p53 gene. When DNA is damaged, it activates p53, which not only
stimulates the DNA repair pathway, but also triggers the synthesis
of proteins that stop cells from dividing before problems are
fixed, she said. In cases where the damage is irreparable, p53
initiates apoptosis, a process of programmed cell death.

In PNAS, Shandilya and colleagues report that for normal
transcription to occur, TFIIB must undergo a process called
phosphorylation, in which a phosphate group is attached to the
protein.

But when the scientists studied cells treated with DNA damaging
agents, they found that TFIIB was dephosphorylated, preventing
general transcription and enabling the cells to focus resources on
helping p53 carry out its tumor suppressing functions. In essence,
p53 can bypass the need for TFIIB phosphorylation to activate
transcription of its target genes, which are vital for DNA damage
response.

Shandilya's colleagues on the PNAS paper are Yuming Wang,
currently working at Cancer Research UK, and Stefan Roberts,
assistant professor of biological sciences. Roberts oversaw the
study, with funding from the National Institute of General Medical
Sciences, one of the National Institutes of Health.

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